Mus musculus strain:C57BL/6 | isolate:non-nicotine-2 | breed:B6.129P2-Apoetm1Unc/J | cultivar:non-nic Raw sequence reads. Mus musculus strain:C57BL/6 | isolate:non-nicotine-2 | breed:B6.129P2-Apoetm1Unc/J | cultivar:non-nic

Electronic cigarettes or electronic nicotine delivery systems (ENDS) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both in smokers and people who have never smoked. To study the cardiac effect of ENDS, I used ApoE knockout (ApoE KO) mice, the most commonly used murine model to study the cardiovascular effects of conventional cigarettes. ApoE KO mice on a western diet (WD) were exposed to saline, ENDS without nicotine (ENDS (0%)) and ENDS with 2.4% nicotine (ENDS (2.4%)) aerosol for 12 weeks. Our preliminary data shows that mice exposed to ENDS (2.4%) have increased levels of serum FFA in comparison with Saline and ENDS (0%). Additionally, ENDS (2.4%) induce a decreased fractional shortening and increased oxidative stress in ApoE KO mice. A transcriptomic analysis of the ENDS (2.4%) treated ApoE KO mice model shows a change in genes associated with metabolism and inflammation.Oxidative stress play a major role in the inflammatory, metabolic and contractile changes of the dysfunctional heart. While there are several sources of reactive oxygen species (ROS), it is generally accepted that the dysfunctional mitochondria is the major source of ROS overproduction. Mitochondrial dysfunction and reduced NAD+ levels are implicated in various metabolic and cardiovascular pathologies. NAD+ is a central metabolic co-factor by virtue of its redox capacity, and as such, regulates a wealth of metabolic transformations and ROS production. Animal models for obesity and smoking have shown decreased levels of NAD+. Nicotinamide riboside (NR), a newly identified precursor of NAD+, increases NAD+ and protects mice against mitochondrial dysfunction and HFD-induced metabolic abnormalities.In this grant resubmission, I hypothesize that correcting mitochondrial abnormalities will produce a protective effect against ENDS induced cardiac dysfunction in the ApoE KO model. During this postdoctoral training, I will pursue the following aims: In Aim 1, I will characterize the effects of ENDS on ROS production, alterations in mitochondrial abnormalities and NAD+ levels associated with cardiac dysfunction. In Aim 2, I will evaluate the effects of NR on oxidative stress, mitochondrial abnormalities, and cardiac dysfunction induced by ENDS